title: Amyotrophic lateral sclerosis: an update on recent genetic insights.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting both upper and lower motor neurons. The prognosis for ALS is extremely poor, but there is a limited course of treatment with only one approved medication. A most striking recent discovery is that TDP-43 is identified as a key molecule that is associated with both sporadic and familial forms of ALS. TDP-43 is not only a pathological hallmark, but also a genetic cause for ALS. Subsequently, a number of ALS-causative genes have been found. Above all, the RNA-binding protein, such as FUS, TAF15, EWSR1 and hnRNPA1, have structural and functional similarities to TDP-43, and physiological functions of some molecules, including VCP, UBQLN2, OPTN, FIG4 and SQSTM1, are involved in a protein degradation system. These discoveries provide valuable insight into the pathogenesis of ALS, and open doors for developing an effective disease-modifying therapy.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Iguchi
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ikenaka
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ishigaki
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D000067528:Ataxins; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins / Q000235:genetics; D003605:D-Amino-Acid Oxidase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases; D051304:Profilins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000235:genetics; D017480:Receptors, sigma / Q000235:genetics; D035582:Transcription Factor TFIIIA / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics; D000074405:Valosin Containing Protein; D000097605:Sigma-1 Receptor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000067528:Ataxins; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D003605:D-Amino-Acid Oxidase; D004268:DNA-Binding Proteins; D005420:Flavoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010744:Phosphoric Monoester Hydrolases; D051304:Profilins; D011506:Proteins; D034702:RNA-Binding Protein FUS; D017480:Receptors, sigma; D035582:Transcription Factor TFIIIA; D014452:Ubiquitins; D000074405:Valosin Containing Protein; D000097605:Sigma-1 Receptor; C568651:C9orf72 protein, human; C409460:OPTN protein, human; C495738:PFN1 protein, human; C520412:SPG11 protein, human; C405662:UBQLN2 protein, human; C417983:DAO protein, human; C522215:FIG4 protein, human; C000614178:VCP protein, human; C000614179:Vcp protein, mouse